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1. UniCoN: Universal Conditional Networks for Multi-Age Embryonic Cartilage Segmentation with Sparsely Annotated Data

Author

Sapkota, Nishchal, Zhang, Yejia, Zhao, Zihao, Gomez, Maria, Hsi, Yuhan, Wilson, Jordan A., Kawasaki, Kazuhiko, Holmes, Greg, Wu, Meng, Jabs, Ethylin Wang, Richtsmeier, Joan T., Perrine, Susan M. Motch, and Chen, Danny Z.

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Osteochondrodysplasia, affecting 2-3% of newborns globally, is a group of bone and cartilage disorders that often result in head malformations, contributing to childhood morbidity and reduced quality of life. Current research on this disease using mouse models faces challenges since it involves accurately segmenting the developing cartilage in 3D micro-CT images of embryonic mice. Tackling this segmentation task with deep learning (DL) methods is laborious due to the big burden of manual image annotation, expensive due to the high acquisition costs of 3D micro-CT images, and difficult due to embryonic cartilage's complex and rapidly changing shapes. While DL approaches have been proposed to automate cartilage segmentation, most such models have limited accuracy and generalizability, especially across data from different embryonic age groups. To address these limitations, we propose novel DL methods that can be adopted by any DL architectures -- including CNNs, Transformers, or hybrid models -- which effectively leverage age and spatial information to enhance model performance. Specifically, we propose two new mechanisms, one conditioned on discrete age categories and the other on continuous image crop locations, to enable an accurate representation of cartilage shape changes across ages and local shape details throughout the cranial region. Extensive experiments on multi-age cartilage segmentation datasets show significant and consistent performance improvements when integrating our conditional modules into popular DL segmentation architectures. On average, we achieve a 1.7% Dice score increase with minimal computational overhead and a 7.5% improvement on unseen data. These results highlight the potential of our approach for developing robust, universal models capable of handling diverse datasets with limited annotated data, a key challenge in DL-based medical image analysis.

Published
2024

2. Global Benchmark Database

Author

Iser, Markus and Jabs, Christoph

Subjects
Computer Science - Databases, Computer Science - Artificial Intelligence, Computer Science - Logic in Computer Science
Abstract

This paper presents Global Benchmark Database (GBD), a comprehensive suite of tools for provisioning and sustainably maintaining benchmark instances and their metadata. The availability of benchmark metadata is essential for many tasks in empirical research, e.g., for the data-driven compilation of benchmarks, the domain-specific analysis of runtime experiments, or the instance-specific selection of solvers. In this paper, we introduce the data model of GBD as well as its interfaces and provide examples of how to interact with them. We also demonstrate the integration of custom data sources and explain how to extend GBD with additional problem domains, instance formats and feature extractors.

Published
2024
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4. ConUNETR: A Conditional Transformer Network for 3D Micro-CT Embryonic Cartilage Segmentation

Author

Sapkota, Nishchal, Zhang, Yejia, Perrine, Susan M. Motch, Hsi, Yuhan, Li, Sirui, Wu, Meng, Holmes, Greg, Abdulai, Abdul R., Jabs, Ethylin W., Richtsmeier, Joan T., and Chen, Danny Z

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Studying the morphological development of cartilaginous and osseous structures is critical to the early detection of life-threatening skeletal dysmorphology. Embryonic cartilage undergoes rapid structural changes within hours, introducing biological variations and morphological shifts that limit the generalization of deep learning-based segmentation models that infer across multiple embryonic age groups. Obtaining individual models for each age group is expensive and less effective, while direct transfer (predicting an age unseen during training) suffers a potential performance drop due to morphological shifts. We propose a novel Transformer-based segmentation model with improved biological priors that better distills morphologically diverse information through conditional mechanisms. This enables a single model to accurately predict cartilage across multiple age groups. Experiments on the mice cartilage dataset show the superiority of our new model compared to other competitive segmentation models. Additional studies on a separate mice cartilage dataset with a distinct mutation show that our model generalizes well and effectively captures age-based cartilage morphology patterns., Comment: Published in ISBI 2024

Published
2024

6. Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Author

Park, Han-Sol, Yin, Anna, Barranta, Caelan, Lee, John, Caputo, Christopher, Sachithanandham, Jaiprasath, Li, Maggie, Yoon, Steve, Sitaras, Ioannis, Jedlicka, Anne, Eby, Yolanda, Ram, Malathi, Fernandez, Reinaldo, Baker, Owen, Shenoy, Aarthi, Mosnaim, Giselle, Fukuta, Yuriko, Patel, Bela, Heath, Sonya, Levine, Adam, Meisenberg, Barry, Spivak, Emily, Anjan, Shweta, Huaman, Moises, Blair, Janis, Zand, Martin, Cachay, Edward, Raval, Jay, Kassaye, Seble, Marshall, Christi, Yarava, Anusha, Lane, Karen, McBee, Nichol, Gawad, Amy, Karlen, Nicky, Singh, Atika, Ford, Daniel, Jabs, Douglas, Appel, Lawrence, Shade, David, Lau, Bryan, Ehrhardt, Stephan, Baksh, Sheriza, Shapiro, Janna, Ou, Jiangda, Na, Yu, Knoll, Maria, Ornelas-Gatdula, Elysse, Arroyo-Curras, Netzahualcoyotl, Gniadek, Thomas, Caturegli, Patrizio, Wu, Jinke, Ndahiro, Nelson, Betenbaugh, Michael, Hanley, Daniel, Casadevall, Arturo, Shoham, Shmuel, Bloch, Evan, Gebo, Kelly, Tobian, Aaron, Laeyendecker, Oliver, Pekosz, Andrew, Klein, Sabra, Sullivan, David, Paxton, James, Gerber, Jonathan, Petrini, Joann, Broderick, Patrick, Rausch, William, Cordisco, Marie, Hammel, Jean, Greenblatt, Benjamin, Cluzet, Valerie, Cruser, Daniel, Oei, Kevin, Abinante, Matthew, Hammitt, Laura, Sutcliffe, Catherine, Currier, Judith, Forthal, Donald, and Ziman, Alyssa

Subjects
COVID-19, Immunoglobulins, Immunotherapy, Humans, COVID-19, COVID-19 Serotherapy, Antibodies, Viral, Immunization, Passive, Hospitalization, SARS-CoV-2, Male, Female, Middle Aged, Adult, Immunoglobulin G, Antibodies, Neutralizing, Double-Blind Method, Aged, Blood Donors, Outpatients
Abstract

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Published
2024

10. Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption

Author

Arielle S. Strasser, Ana Silvia Gonzalez-Reiche, Xianxiao Zhou, Braulio Valdebenito-Maturana, Xiaoqian Ye, Bin Zhang, Meng Wu, Harm van Bakel, and Ethylin Wang Jabs

Subjects
Science
Abstract

Abstract Roberts syndrome (RBS) is an autosomal recessive disorder with profound growth deficiency and limb reduction caused by ESCO2 loss-of-function variants. Here, we elucidate the pathogenesis of limb reduction in an Esco2 fl/fl;Prrx1-Cre Tg/0 mouse model using bulk- and single-cell-RNA-seq and gene co-expression network analyses during embryogenesis. Our results reveal morphological and vascular defects culminating in hemorrhage of mutant limbs at E12.5. Underlying this abnormal developmental progression is a pre-apoptotic, mesenchymal cell population specific to mutant limb buds enriched for p53-related signaling beginning at E9.5. We then characterize these p53-related processes of cell cycle arrest, DNA damage, cell death, and the inflammatory leukotriene signaling pathway in vivo. In utero treatment with pifithrin-α, a p53 inhibitor, rescued the hemorrhage in mutant limbs. Lastly, significant enrichments were identified among genes associated with RBS, thalidomide embryopathy, and other genetic limb reduction disorders, suggesting a common vascular etiology among these conditions.

Published
2024
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11. A Retrospective Analysis of Diagnostic Breast Imaging Outcomes in Young Women at a Tertiary Care Center

Author

Navdeep Dehar, Doris Jabs, Wilma Hopman, and Mihaela Mates

Subjects
breast cancer, young women, screening, diagnostic mammogram, ultrasound, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

(1) Purpose: The purpose of this study was to describe the outcomes of diagnostic breast imaging and the incidence of delayed breast cancer diagnosis in the study population. (2) Methods: We collected the outcome data from diagnostic mammograms and/or breast ultrasounds (USs) performed on women between the ages of 30 and 50 with symptomatic breast clinical presentations between 2018 and 2019. (3) Results: Out of 171 eligible patients, 10 patients (5.8%) had BIRADS 0, 90 patients (52.6%) had benign findings (BIRADS 1 and 2), 41 (24.0%) patients had probable benign findings requiring short-term follow-up (BIRADS 3), while 30 (17.5%) patients had findings suspicious of malignancy (BIRADS 4 and 5). In the BIRADS 3 group, 92.7% had recommended follow-up, while in BIRADS 4 and 5, only 83.3% underwent recommended biopsy at a mean time of 1.7 weeks (range 0–22 wks) from their follow-up scan. Ten (6%) patients were diagnosed with breast cancer, all of whom had BIRADS 4 or 5, with a mean time of breast cancer diagnosis from initial diagnostic imaging of 2.2 weeks (range 1–22 wks). No patients had delayed breast cancer diagnosis in our cohort. (4) Conclusions: We conclude that diagnostic mammograms and breast US are appropriate investigations for clinical breast concerns in women aged 30–50 years.

Published
2024
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12. Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange

Author

Albert, Annemarie, Bramstedt, Jörn, Brand, Marcus, Brinkkötter, Paul T., Cukoski, Sadrija, Eichenauer, Dennis A., Elitok, Saban, Felten, Helmut, Gäckler, Anja, Geuther, Gesa, Harth, Ana, Hausberg, Martin, Hermann, Matthias, Hinkel, Ulrich P., Jabs, Wolfram Johannes, Kaufeld, Jessica, Klein, Gilles, Klemm, Kristin, Kolbrink, Benedikt, Kühne, Lucas, Menne, Jan, Miesbach, Wolfgang, Mühlfeld, Anja Susanne, Özcan, Fedai, Osterholt, Thomas, Pfrepper, Christian, Potthoff, Sebastian A., Radermacher, Jörg, Ruhe, Johannes, Schmidt, Tilman, Schönermarck, Ulf, Schönfelder, Kristina, Schreiber, Adrian, Schulte, Kevin, Schulte-Kemna, Lena, Schwenger, Vedat, Seelow, Evelyn, Seibert, Felix S., Todorova, Polina, Tölle - Charité, Markus, Völker, Linus A., Walendy, Victor, Wendt, Ralph, Westhoff, Timm H., Knöbl, Paul, Eller, Kathrin, Thaler, Johannes, Sperr, Wolfgang R., Gleixner, Karoline, Buxhofer-Ausch, Veronika, Mühlfeld, Anja, Jabs, Wolfram J., Westhoff, Timm, and Brinkkoetter, Paul T.

Published
2024
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13. Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis

Author

Tenney, Alan P, Di Gioia, Silvio Alessandro, Webb, Bryn D, Chan, Wai-Man, de Boer, Elke, Garnai, Sarah J, Barry, Brenda J, Ray, Tammy, Kosicki, Michael, Robson, Caroline D, Zhang, Zhongyang, Collins, Thomas E, Gelber, Alon, Pratt, Brandon M, Fujiwara, Yuko, Varshney, Arushi, Lek, Monkol, Warburton, Peter E, Van Ryzin, Carol, Lehky, Tanya J, Zalewski, Christopher, King, Kelly A, Brewer, Carmen C, Thurm, Audrey, Snow, Joseph, Facio, Flavia M, Narisu, Narisu, Bonnycastle, Lori L, Swift, Amy, Chines, Peter S, Bell, Jessica L, Mohan, Suresh, Whitman, Mary C, Staffieri, Sandra E, Elder, James E, Demer, Joseph L, Torres, Alcy, Rachid, Elza, Al-Haddad, Christiane, Boustany, Rose-Mary, Mackey, David A, Brady, Angela F, Fenollar-Cortés, María, Fradin, Melanie, Kleefstra, Tjitske, Padberg, George W, Raskin, Salmo, Sato, Mario Teruo, Orkin, Stuart H, Parker, Stephen CJ, Hadlock, Tessa A, Vissers, Lisenka ELM, van Bokhoven, Hans, Jabs, Ethylin Wang, Collins, Francis S, Pennacchio, Len A, Manoli, Irini, and Engle, Elizabeth C

Subjects
Biological Sciences, Genetics, 2.1 Biological and endogenous factors, Animals, Mice, Facial Paralysis, GATA2 Transcription Factor, Motor Neurons, Neurogenesis, Neurons, Efferent, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

Published
2023

14. Heterogeneous material models for finite element analysis of the human mandible bone – A systematic review

Author

Iman Soodmand, Ann-Kristin Becker, Jan-Oliver Sass, Christopher Jabs, Maeruan Kebbach, Gesa Wanke, Michael Dau, and Rainer Bader

Subjects
Personalized finite element model, Mandible, Heterogeneous mechanical properties, Hounsfield units, Density, Elastic modulus, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Subject-specific finite element (FE) modeling of the mandible bone has recently gained attention for its higher accuracy. A critical modeling factor is including personalized material properties from medical images especially when bone quality has to be respected. However, there is no consensus on the material model for the mandible that realistically estimates the Young's modulus of the bone. Therefore, the present study aims to review FE studies employing heterogeneous material modeling of the human mandible bone, synthesizing these models, investigating their origins, and assessing their risk of bias.A systematic review using PRISMA guidelines was conducted on publications before 1st July 2024, involving PubMed, Scopus, and Web of Science. The search string considered (a) anatomical site (b) modeling strategy, and (c) metrics of interest. Two inclusion and five exclusion criteria were defined.A review of 77 FE studies identified 12 distinct heterogeneous material models, built based on different in vitro or computational methodologies leading to varied performance and highly deviated range of estimated Young's modulus. They are proposed for bones from five different anatomical sites than mandible and for both trabecular and cortical bone domains. The original studies were characterized with a low to medium risk of bias.This review assessed the current state of material modeling for subject-specific FE models in the craniomaxillofacial field. Recommendations are provided to support researchers in selecting density-modulus relationships. Future research should focus on standardizing experimental protocols, validating models through combined simulation and experimental approaches, and investigating the anisotropic behaviour of the mandible bone.

Published
2024
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15. Activity dependent modulation of glial gap junction coupling in the thalamus

Author

Paula Baum, Anna Beinhauer, Lara Zirwes, Linda Loenneker, Ronald Jabs, Rajeevan T. Narayanan, Marcel Oberlaender, Gerald Seifert, Helmut Kettenmann, and Christian Steinhäuser

Subjects
molecular neuroscience, cellular neuroscience, Science
Abstract

Summary: Astrocytes and oligodendrocytes in the ventrobasal thalamus are electrically coupled through gap junctions. We have previously shown that these cells form large panglial networks, which have a key role in the transfer of energy substrates to postsynapses for sustaining neuronal activity. Here, we show that the efficiency of these transfer networks is regulated by synaptic activity: preventing the generation and propagation of action potentials resulted in reduced glial coupling. Systematic analyses of mice deficient for individual connexin isoforms revealed that oligodendroglial Cx32 and Cx47 are the targets of this modulation. Importantly, we show that during a critical time window, sensory deprivation through whisker trimming reduces the efficiency of the glial transfer networks also in vivo. Together with our previous results the current findings indicate that neuronal activity and provision of energy metabolites through panglial coupling are interdependent events regulated in a bidirectional manner.

Published
2024
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20. Knowledge Management in SMEs: Applying Link Prediction for Assisted Decision Making

Author

Lehmann, Steven, Schließer, Jörg, Schumann, Sandra, Winkler, Heiner, Jabs, Iren, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Villmann, Thomas, editor, Kaden, Marika, editor, Geweniger, Tina, editor, and Schleif, Frank-Michael, editor

Published
2024
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21. Core Boosting in SAT-Based Multi-objective Optimization

Author

Jabs, Christoph, Berg, Jeremias, Järvisalo, Matti, Goos, Gerhard, Series Editor, Hartmanis, Juris, Founding Editor, van Leeuwen, Jan, Series Editor, Hutchison, David, Editorial Board Member, Kanade, Takeo, Editorial Board Member, Kittler, Josef, Editorial Board Member, Kleinberg, Jon M., Editorial Board Member, Kobsa, Alfred, Series Editor, Mattern, Friedemann, Editorial Board Member, Mitchell, John C., Editorial Board Member, Naor, Moni, Editorial Board Member, Nierstrasz, Oscar, Series Editor, Pandu Rangan, C., Editorial Board Member, Sudan, Madhu, Series Editor, Terzopoulos, Demetri, Editorial Board Member, Tygar, Doug, Editorial Board Member, Weikum, Gerhard, Series Editor, Vardi, Moshe Y, Series Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, and Dilkina, Bistra, editor

Published
2024
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22. Data-Codata Symmetry and its Interaction with Evaluation Order

Author

Binder, David, Jabs, Julian, Skupin, Ingo, and Ostermann, Klaus

Subjects
Computer Science - Programming Languages, D.3.1
Abstract

Data types and codata types are, as the names suggest, often seen as duals of each other. However, most programming languages do not support both of them in their full generality, or if they do, they are still seen as distinct constructs with separately defined type-checking, compilation, etc. Rendel et al. were the first to propose variants of two standard program transformations, de- and refunctionalization, as a test to gauge and improve the symmetry between data and codata types. However, in previous works, codata and data were still seen as separately defined language constructs, with de- and refunctionalization being defined as similar but separate algorithms. These works also glossed over interactions between the aforementioned transformations and evaluation order, which leads to a loss of desirable $\eta$ expansion equalities. We argue that the failure of complete symmetry is due to the inherent asymmetry of natural deduction as the logical foundation of the language design. Natural deduction is asymmetric in that its focus is on producers (proofs) of types, whereas consumers (contexts, continuations, refutations) have a second-class status. Inspired by existing sequent-calculus-based language designs, we present the first language design that is fully symmetric in that the issues of polarity (data type vs codata types) and evaluation order (call-by-value vs call-by-name) are untangled and become independent attributes of a single form of type declaration. Both attributes, polarity and evaluation order, can be changed independently by one algorithm each. In particular, defunctionalization and refunctionalization are now one algorithm. Evaluation order can be defined and changed individually for each type, independently from polarity. By allowing only certain combinations of evaluation order and polarity, the aforementioned $\eta$ laws can be restored., Comment: 23 pages, 11 figures

Published
2022

23. The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2—global current practice patterns for the management of Cytomegalovirus anterior uveitis

Author

Thng, Zheng Xian, Putera, Ikhwanuliman, Testi, Ilaria, Chan, Kevin, Westcott, Mark, Chee, Soon-Phaik, Dick, Andrew D., Kempen, John H., Bodaghi, Bahram, Thorne, Jennifer E., Barisani-Asenbauer, Talin, de Smet, Marc D., Smith, Justine R., McCluskey, Peter, La Distia Nora, Rina, Jabs, Douglas A., de Boer, Joke H., Sen, H. Nida, Goldstein, Debra A., Khairallah, Moncef, Davis, Janet L., Rosenbaum, James T., Jones, Nicholas P., Nguyen, Quan Dong, Pavesio, Carlos, Agrawal, Rupesh, and Gupta, Vishali

Published
2024
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24. The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1—global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis

Author

Thng, Zheng Xian, Putera, Ikhwanuliman, Testi, Ilaria, Chan, Kevin, Westcott, Mark, Chee, Soon-Phaik, Dick, Andrew D., Kempen, John H., Bodaghi, Bahram, Thorne, Jennifer E., Barisani-Asenbauer, Talin, de Smet, Marc D., Smith, Justine R., McCluskey, Peter, La Distia Nora, Rina, Jabs, Douglas A., de Boer, Joke H., Sen, H. Nida, Goldstein, Debra A., Khairallah, Moncef, Davis, Janet L., Rosenbaum, James T., Jones, Nicholas P., Nguyen, Quan Dong, Pavesio, Carlos, Agrawal, Rupesh, and Gupta, Vishali

Published
2024
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25. Transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection: a double-blinded, phase 2 randomized, controlled trial

Author

Shoham, Shmuel, Bloch, Evan M, Casadevall, Arturo, Hanley, Daniel, Lau, Bryan, Gebo, Kelly, Cachay, Edward, Kassaye, Seble G, Paxton, James H, Gerber, Jonathan, Levine, Adam C, Naeim, Arash, Currier, Judith, Patel, Bela, Allen, Elizabeth S, Anjan, Shweta, Appel, Lawrence, Baksh, Sheriza, Blair, Paul W, Bowen, Anthony, Broderick, Patrick, Caputo, Christopher A, Cluzet, Valerie, Cordisco, Marie Elena, Cruser, Daniel, Ehrhardt, Stephan, Forthal, Donald, Fukuta, Yuriko, Gawad, Amy L, Gniadek, Thomas, Hammel, Jean, Huaman, Moises A, Jabs, Douglas A, Jedlicka, Anne, Karlen, Nicky, Klein, Sabra, Laeyendecker, Oliver, Lane, Karen, McBee, Nichol, Meisenberg, Barry, Merlo, Christian, Mosnaim, Giselle, Park, Han-Sol, Pekosz, Andrew, Petrini, Joann, Rausch, William, Shade, David M, Shapiro, Janna R, Singleton, J Robinson, Sutcliffe, Catherine, Thomas, David L, Yarava, Anusha, Zand, Martin, Zenilman, Jonathan M, Tobian, Aaron AR, and Sullivan, David J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biodefense, Lung, Pneumonia, Clinical Trials and Supportive Activities, Vaccine Related, Prevention, Infectious Diseases, Emerging Infectious Diseases, Clinical Research, Infection, Good Health and Well Being, Humans, Adolescent, Adult, SARS-CoV-2, COVID-19, Post-Exposure Prophylaxis, COVID-19 Serotherapy, Double-Blind Method, Immunization, Passive, post-exposure-prophylaxis, convalescent plasma, transfusion, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundThe efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.MethodsThis double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection.ResultsIn total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups.ConclusionsAdministration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection.Clinical trials registrationNCT04323800.

Published
2023

31. Contributors

Author

Albokhari, Daniah, primary, Ayoubieh, Houriya, additional, Balwani, Manisha, additional, Barry, Jessica C., additional, Blagowidow, Natalie, additional, Bodurtha, Joann, additional, Bottini, Alexander, additional, Brewer, Takae M., additional, Brodie, Scott, additional, Brown, Emily E., additional, Bush, Lynn Wein, additional, Butterfield, Russell J., additional, Campbell, Kirk, additional, Clemens, Douglas K., additional, Corson, Virginia L., additional, Cytrynbaum, Cheryl, additional, Dedania, Vaidehi, additional, Diaz, George A., additional, Dietz, Harry C., additional, Dinulos, Mary Beth Palko, additional, Eng, Christine M., additional, Eng, Charis, additional, Fan, Audrey L., additional, Francomano, Clair A., additional, Frucht, Steven J., additional, Ganesh, Jaya, additional, Gelb, Bruce D., additional, Goduni, Lediana, additional, Gu, Shen, additional, Gupta, Isha, additional, Hagerman, Randi J., additional, Hall, Judith G., additional, Hoover-Fong, Julie, additional, Hudgins, Louanne, additional, Iverson, Ayuko, additional, Jabs, Ethylin Wang, additional, James, Cynthia A., additional, Jari, Shama, additional, Keppler-Noreuil, Kim M., additional, Kerr, Lynne M., additional, Kimball, Amy, additional, Kline, Antonie D., additional, Kline, Joel N., additional, Kritzer, Amy, additional, Lambert, Michele P., additional, Lew, Cheryl D., additional, Li, Shao-Tzu, additional, MacCarrick, Gretchen, additional, Matalon, Dena R., additional, McDonald-McGinn, Donna M., additional, McMahon, Francis J., additional, Meliambro, Kristin, additional, Moore, Rebekah A., additional, Murray, Brittney, additional, Newcomb, Tara, additional, Ngeow, Joanne, additional, Ogawa, Jessica, additional, Patel, Dhruv K., additional, Pollin, Toni I., additional, Prasun, Pankaj, additional, Puliaiev, Maksym, additional, Pyeritz, Reed E., additional, Rasmussen, Sonja A., additional, Riboldi, Giulietta Maria, additional, Schecter, Scott M., additional, Scheuerle, Angela E., additional, Scott, Stuart A., additional, Shankar, Suma, additional, Slavotinek, Anne, additional, Smith-Hicks, Constance L., additional, Stewart, Rosalyn W., additional, Trandafir, Cristina, additional, Triano, Vivian Narcisa, additional, Vernon, Hilary J., additional, Wasserstein, Melissa P., additional, Webb, Bryn D., additional, Weksberg, Rosanna, additional, and Yuan, Bo, additional

Published
2024
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35. Using the Forest Maturity Index to model understory regeneration of post-agricultural forest in the NE Carpathians

Author

Zofia Jabs-Sobocińska, Andrzej N. Affek, and Jan Marek Matuszkiewicz

Subjects
Post-agricultural forests, Understory regeneration, Ancient forest species, Forest Maturity Index, Multiple regression model, Topographic factors, Ecology, QH540-549.5
Abstract

The regeneration dynamics of understory vegetation in recent forests, arising from extensive agricultural land abandonment, is closely related to soil properties and proximity to ancient forests. However, the role of topography in shaping this regeneration process, especially in mountainous regions, remains unclear.This study addresses this gap by investigating the regeneration rate of understory vegetation in mountainous recent forests within the NE Carpathians, a region profoundly shaped by large-scale population displacements in the 1940s, leading to widespread agricultural land abandonment and the subsequent development of new forests.We quantified the understory regeneration rate of recent forests through extensive phytosociological relevé surveys conducted in one vegetation season. Data were collected from 194 randomly selected plots of recent forests and 100 plots of ancient forests, each exhibiting diverse topographic characteristics. By calculating the Forest Maturity Index based on ancient forest species and employing a parametrized multiple regression model, we identified key factors influencing the understory regeneration process. We further used the obtained regression formula to model the forest regeneration rate across the entire study area (40,975 ha).Proximity to ancient forests positively influenced understory regeneration. Elevation and slope also emerged as significant determinants, with the understory regeneration rate decreasing with elevation and increasing with slope steepness. Furthermore, a higher cover of pine in the tree stand had a suppressive effect. The above-mentioned dependencies resulted in substantial variations in the modeled understory regeneration of post-agricultural forests.The utilization of the Forest Maturity Index offers invaluable insights into identifying and subsequently safeguarding well-regenerated forests. Given the prevalence of forest secondary succession in various regions, this index emerges as a key indicator for future assessments and management strategies.

Published
2024
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39. Incidence and Remission of Post‐Surgical Cystoid Macular Edema Following Cataract Surgery in Eyes With Intraocular Inflammation

Author

Gangaputra, Sapna, Newcomb, Craig, Ying, Gui-Shuang, Groth, Sylvia, Fitzgerald, Tonetta D., Artornsombudh, Pichaporn, Kothari, Srishti, Pujari, Siddharth S., Jabs, Douglas A., Levy-Clarke, Grace A., Nussenblatt, Robert B., Rosenbaum, James T., Sen, H. Nida, Suhler, Eric B., Thorne, Jennifer E., Bhatt, Nirali P., Foster, C. Stephen, Dreger, Kurt A., Buchanich, Jeanine M., and Kempen, John H.

Published
2024
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42. Informing pandemic management in Germany with trustworthy living evidence syntheses and guideline development: lessons learned from the COVID-19 evidence ecosystem

Author

Kunzler, Angela M., Iannizzi, Claire, Burns, Jacob, Metzendorf, Maria-Inti, Voigt-Radloff, Sebastian, Piechotta, Vanessa, Schmaderer, Christoph, Holzmann-Littig, Christopher, Balzer, Felix, Benstoem, Carina, Binder, Harald, Boeker, Martin, Dirnagl, Ulrich, Fichtner, Falk, Golinski, Martin, Grundmann, Hajo, Hengel, Hartmut, Jabs, Jonas, Kern, Winfried V., Kopp, Ina, Kranke, Peter, Kreuzberger, Nina, Laudi, Sven, Lichtner, Gregor, Lieb, Klaus, Maun, Andy, Moerer, Onnen, Müller, Anika, Mutters, Nico T., Nothacker, Monika, Pfadenhauer, Lisa M., Popp, Maria, Rüschemeyer, Georg, Schmucker, Christine, Schwingshackl, Lukas, Spies, Claudia, Steckelberg, Anke, Stegemann, Miriam, Strech, Daniel, von Dincklage, Falk, Weibel, Stephanie, Wunderlich, Maximilian Markus, Zöller, Daniela, Rehfuess, Eva, Skoetz, Nicole, and Meerpohl, Joerg J.

Published
2024
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43. Association of Intermediate-Stage Age-Related Macular Degeneration with Plasma Inflammatory Biomarkers in Persons with AIDS

Author

Douglas A. Jabs, MD, MBA, Michael F. Schneider, MS, Jeong Won Pak, PhD, Gabriele Beck-Engeser, B.Sc, Fay Chan, Gabrielle C. Ambayec, and Peter W. Hunt, MD

Subjects
Acquired immunodeficiency syndrome, Age-related macular degeneration, Biomarkers, Cataract, Inflammation, Ophthalmology, RE1-994
Abstract

Purpose: To evaluate associations of plasma levels of inflammatory biomarkers with age-related macular degeneration (AMD) and cataract in persons with AIDS. Design: Nested case–control study (analysis 1) and nested cohort study (analysis 2). Participants: Analysis 1: persons with AIDS and incident intermediate-stage AMD (n = 26) and controls without AMD matched for age, race/ethnicity, and gender (n = 49) from The Longitudinal Study of Ocular Complications of AIDS. Analysis 2: 475 persons from LSOCA with baseline plasma biomarker levels followed prospectively for cataract. Methods: In both analyses, cryopreserved plasma specimens obtained at baseline were assayed for monocyte chemoattractant protein (MCP)-1 (CC motif chemokine ligand [CCL] 2), macrophage inflammatory protein (MIP)-1β (CCL4), soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, and fractalkine (CX3 motif chemokine ligand 1 [CX3CL1]). Main Outcome Measures: Analysis 1: mean difference (cases − controls) in plasma biomarker levels. Analysis 2: incident cataract. Results: After adjusting for plasma human immunodeficiency virus RNA level, CD4+ T-cell count, and smoking, elevated baseline plasma levels of sTNFR2 and IL-18 (mean differences [cases − controls] 0.11 log10[pg/mL]; 95% confidence interval [CI], 0.01–0.20; P = 0.024 and 0.13 log10[pg/mL]; 95% CI, 0.01–0.24; P = 0.037, respectively) each were associated with incident AMD. In a competing risk (with mortality) analysis, elevated baseline standardized log10 plasma levels of MCP-1, sTNFR2, IL-18, and fractalkine each were associated with a decreased cataract risk. Conclusions: When combined with previous data suggesting that AMD is associated with elevated plasma levels of C-reactive protein, soluble CD14, and possibly IL-6, the association of elevated plasma levels of sTNFR2 and IL-18 with incident AMD, but not with incident cataract, suggests that innate immune system activation, and possibly NLRP3 inflammasome activation, may play a role in the pathogenesis of AMD in this population. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Published
2024
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44. Early Outpatient Treatment for Covid-19 with Convalescent Plasma

Author

Sullivan, David J, Gebo, Kelly A, Shoham, Shmuel, Bloch, Evan M, Lau, Bryan, Shenoy, Aarthi G, Mosnaim, Giselle S, Gniadek, Thomas J, Fukuta, Yuriko, Patel, Bela, Heath, Sonya L, Levine, Adam C, Meisenberg, Barry R, Spivak, Emily S, Anjan, Shweta, Huaman, Moises A, Blair, Janis E, Currier, Judith S, Paxton, James H, Gerber, Jonathan M, Petrini, Joann R, Broderick, Patrick B, Rausch, William, Cordisco, Marie-Elena, Hammel, Jean, Greenblatt, Benjamin, Cluzet, Valerie C, Cruser, Daniel, Oei, Kevin, Abinante, Matthew, Hammitt, Laura L, Sutcliffe, Catherine G, Forthal, Donald N, Zand, Martin S, Cachay, Edward R, Raval, Jay S, Kassaye, Seble G, Foster, E Colin, Roth, Michael, Marshall, Christi E, Yarava, Anusha, Lane, Karen, McBee, Nichol A, Gawad, Amy L, Karlen, Nicky, Singh, Atika, Ford, Daniel E, Jabs, Douglas A, Appel, Lawrence J, Shade, David M, Ehrhardt, Stephan, Baksh, Sheriza N, Laeyendecker, Oliver, Pekosz, Andrew, Klein, Sabra L, Casadevall, Arturo, Tobian, Aaron AR, and Hanley, Daniel F

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Clinical Trials and Supportive Activities, Neurodegenerative, Patient Safety, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Ambulatory Care, COVID-19, Disease Progression, Double-Blind Method, Hospitalization, Humans, Immunization, Passive, Treatment Outcome, United States, COVID-19 Serotherapy, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPolyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.MethodsIn this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion.ResultsParticipants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized.ConclusionsIn participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

Published
2022

45. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Author

Salluzzi, Marina, Blenkin, Nicole, Dueck, Ashley, Doram, Craig, Zhang, Qiao, Kenney, Carol, Ryckborst, Karla, Bohn, Shelly, Collier, Quentin, Taylor, Frances, Lethebe, B. Cord, Jambula, Anitha, Sage, Kayla, Toussaint, Lana, Save, Supryia, Lee, Jaclyn, Laham, N, Sultan, A.A., Deepak, A., Sitaram, A., Demchuk, Andrew M., Lockey, A., Micielli, A., Wadhwa, A., Arabambi, B., Graham, B., Bogiatzi, Chrysi, Doshi, Darshan, Chakraborty, D., Kim, Diana, Vasquez, D, Singh, D, Tse, Dominic, Harrison, E., Smith, E.E., Teleg, E., Klourfeld, E., Klein, G., Sebastian, I.A., Evans, J, Hegedus, J, Kromm, J, Lin, K, Ignacio, K, Ghavami, Kimia, Ismail, M., Moores, M., Panzini, M.A., Boyko, M., Almekhlafi, M.A., Newcommon, Nancy, Maraj, N., Imoukhuede, O., Volny, O., Stys, Peter, Couillard, Phillipe, Ojha, P., Eswaradass, P., Joundi, Raed, Singh, R., Asuncion, R.M., Muir, R.T., Dey, S., Mansoor, S., Wasyliw, S., Nagendra, S., Hu, Sherry, Althubait, S., Chen, S., Bal, S., Van Gaal, Stephen, Peters, Steven, Ray, Sucharita, Chaturvedi, S., Subramaniam, Suresh, Fu, Vivian, Villaluna, K., Maclean, G., King-Azote, P., Ma, C., Plecash, A., Murphy, C., Gorman, J., Wilson, L., Zhou, L., Benevente, O., Teal, P., Yip, S., Mann, S., Dewar, B., Demetroff, M., Shamloul, R., Beardshaw, R., Roberts, S., Blaquiere, D., Stotts, G., Shamy, M., Bereznyakova, O., Fahed, R., Alesefir, W., Lavoie, Suzy, Hache, A., Collard, K, Mackey, A., Gosselin-Lefebvre, S., Verreault, S., Beauchamp, B., Lambourn, L., Khaw, A., Mai, L., Sposato, L., Bres Bullrich, M., Azarpazhooh, R., Fridman, S., Kapoor, A., Southwell, A., Bardi, E., Fatakdawala, I., Kamra, M, Lopes, K., Popel, N., Norouzi, V., Liu, A., Liddy, A.M., Ghoari, B., Hawkes, C., Enriquez, C.A., Gladstone, D.J., Manosalva Alzate, H.A., Khosravani, H., Hopyan, J.J., Sivakumar, K., Son, M., Boulos, M.I., Hamind, M.A., Swartz, R.H., Murphy, R., Reiter, S., Fitzpatrick, T., Bhandari, V., Good, J., Penn, M., Naylor, M., Frost, S., Cayley, A., Akthar, F., Williams, J., Kalman, L., Crellin, L., Wiegner, R., Singh, R.S., Stewart, T., To, W., Singh, S., Pikula, A., Jaigobin, C., Carpani, F., Silver, F., Janssen, H., Schaafsma, J., del Campo, M., Alskaini, M., Rajendram, P., Fairall, P., Granfield, B., Crawford, D., Jabs, J., White, L., Sivakumar, L., Piquette, L., Nguyen, T., Nomani, A., Wagner, A., Alrohimi, A., Butt, A., D'Souza, A., Gajurel, B., Vekhande, C., Kamble, H., Kalashyan, H., Lloret, M., Benguzzi, M., Arsalan, N., Ishaque, N., Ashayeriahmadabad, R., Samiento, R., Hosseini, S., Kazi, S., Das, S., Sugumar, T., Selchen, D., Kostyrko, P., Muccilli, A., Saposnik, A.G., Vandervelde, C., Ratnayake, K., McMillan, S., Katsanos, A., Shoamanesh, A., Sahlas, D.J., Naidoo, V., Todorov, V., Toma, H., Brar, J., Lee, J., Horton, M., Shand, E., Weatherby, S., Jin, A., Durafourt, B., Jalini, S., Gardner, A., Tyson, C., Junk, E., Foster, K., Bolt, K., Sylvain, N., Maley, S., Urroz, L., Peeling, L., Kelly, M., Whelan, R., Cooley, R., Teitelbaum, J., Boutayeb, A., Moore, A., Cole, E., Waxman, L., Ben-Amor, N., Sanchez, R., Khalil, S., Nehme, A., Legault, C., Tampieri, D., Ehrensperger, E., Vieira, L., Cortes, M., Angle, M., Hannouche, M., Badawy, M., Werner, K., Wieszmuellner, S., Langer, A., Gisold, A., Zach, H., Rommer, P., Macher, S., Blechinger, S., Marik, W., Series, W., Baumgartinger, M., Krebs, S., Koski, J., Eirola, S., Ivanoff, T., Erakanto, A., Kupari, L., Sibolt, G., Panula, J., Tomppo, L., Tiainen, M., Ahlstrom, M., Martinez Majander, N., Suomalainen, O., Raty, S., Levi, C., Kerr, E., Allen, J., Kaauwai, L.P., Belevski, L., Russell, M., Ormond, S., Chew, A., Loiselle, A., Royan, A., Hughes, B., Garcia Esperon, C., Pepper, E., Miteff, F., He, J., Lycett, M., Min, M., Murray, N., Pavey, N., Starling de Barros, R., Gangadharan, S., Dunkerton, S., Waller, S., Canento Sanchez, T., Wellings, T., Edmonds, G., Whittaker, K.A., Ewing, M., Lee, P., Singkang, R., McDonald, A., Dos Santos, A., Shin, C., Jackson, D., Tsoleridis, J., Fisicchia, L., Parsons, N., Shenoy, N., Smith, S., Sharobeam, A., Balabanski, A., Park, A., Williams, C., Pavlin-Premri, D., Rodrigues, E., Alemseged, F., Ng, F., Zhao, H., Beharry, J., Ng, J.L., Williamson, J., Wong, J.Z.W., Li, K., Kwan, M.K., Valente, M., Yassi, N., Yogendrakumar, V., McNamara, B., Buchanan, C., McCarthy, C., Thomas, G., Stephens, K., Chung, M., Chung, M.F., Tang, M., Busch, T., Frost, T., Lee, R., Stuart, N., Pachani, N., Menon, A., Borojevic, B., Linton, C.M., Garcia, G., Callaly, E.P., Dewey, H., Liu, J., Chen, J., Wong, J., Nowak, K., To, K., Lizak, N.S., Bhalala, O., Park, P., Tan, P., Martins, R., Cody, R., Forbes, R., Chen, S.K., Ooi, S., Tu, S., Dang, Y.L., Ling, Z., Cranefield, J., Drew, R., Tan, A., Kurunawai, C., Harvey, J., Mahadevan, J.J., Cagi, L., Palanikumar, L., Chia, L.N., Goh, R., El-Masri, S., Urbi, B., Rapier, C., Berrill, H., McEvoy, H., Dunning, R., Kuriakose, S., Chad, T., Sapaen, V., Sabet, A., Shah, D., Yeow, D., Lilley, K., Ward, K., Mozhy Mahizhnan, M., Tan, M., Lynch, C., Coveney, S., Tobin, K., McCabe, J., Marnane, M., Murphy, S., Large, M., Moynihan, B., Boyle, K., Sanjuan, E., Sanchis, M., Boned, S., Pancorbo, O., Sala, V., Garcia, L., Garcia-Tornel, A., Juega, J., Pagola, J., Santana, K., Requena, M., Muchada, M., Olive, M., Lozano, P.J., Rubiera, M., Deck, M., Rodriguez, N., Gomez, B., Reyes Munoz, F.J., Gomez, A.S., Sanz, A.C., Garcia, E.C., Penacoba, G., Ramos, M.E., de Lera Alfonso, M., Feliu, A, Pardo, L., Ramirez, P., Murillo, A., Lopez Dominguez, D., Rodriguez, J., Terceno Izaga, M., Reina, M., Viturro, S.B., Bojaryn, U., Vera Monge, V.A., Silva Blas, Y., R Siew, R., Agustin, S J, Seet, C., Tianming, T., d'Emden, A., Murray, A., Welch, A., Hatherley, K., Day, N., Smith, W., MacRae, E., Mitchell, E.S., Mahmood, A., Elliot, J., Neilson, S., Biswas, V., Brown, C., Lewis, A., Ashton, A., Werring, D., Perry, R., Muhammad, R., Lee, Y.C., Black, A., Robinson, A., Williams, A., Banaras, A., Cahoy, C., Raingold, G., Marinescu, M., Atang, N., Bason, N., Francia, N., Obarey, S., Feerick, S., Joseph, J., Schulz, U., Irons, R., Benjamin, J., Quinn, L., Jhoots, M., Teal, R., Ford, G., Harston, G., Bains, H., Gbinigie, I., Mathieson, P., Sim, C.H., Hayter, E., Kennedy, K., Binnie, L., Priestley, N., Williams, R., Ghatala, R., Stratton, S., Blight, A., Zhang, L., Davies, A., Duffy, H., Roberts, J., Homer, J., Roberts, K., Dodd, K., Cawley, K., Martin, M., Leason, S., Cotgreave, S., Taylor, T., Nallasivan, A., Haider, S., Chakraborty, T., Webster, T., Gil, A., Martin, B., Joseph, B., Cabrera, C., Jose, D., Man, J., Aquino, J., Sebastian, S., Osterdahl, M., Kwan, M., Matthew, M., Ike, N., Bello, P., Wilding, P., Fuentes, R., Shah, R., Mashate, S., Patel, T., Nwanguma, U., Dave, V., Haber, A., Lee, A., O'Sullivan, A., Drumm, B., Dawson, A.C., Matar, T., Roberts, D., Taylor, E., Rounis, E., El-Masry, A., O'Hare, C., Kalladka, D., Jamil, S., Auger, S., Raha, O., Evans, M., Vonberg, F., Kalam, S., Ali Sheikh, A., Jenkins, I.H., George, J., Kwan, J., Blagojevic, J., Saeed, M., Haji-Coll, M., Tsuda, M., Sayed, M., Winterkron, N., Thanbirajah, N., Vittay, O., Karim, R., Smail, R.C., Gauhar, S., Elmamoun, S., Malani, S., Pralhad Kelavkar, S., Hiden, J., Ferdinand, P., Sanyal, R., Varquez, R., Smith, B., Okechukwu, C., Fox, E., Collins, E., Courtney, K., Tauro, S., Patterson, C., McShane, D., Roberts, G., McIImoyle, J., McGuire, K., Fearon, P., Gordon, P., Isaacs, K., Lucas, K., Smith, L., Dews, L., Bates, M., Lawrence, S., Heeley, S., Patel, V., Chin, Y.M., Sims, D., Littleton, E., Khaira, J., Nadar, K., Kieliszkowska, A., Sari, B., Domingos Belo, C., Smith, E., Manolo, E.Y., Aeron-Thomas, J., Doheny, M., Garcia Pardo, M., Recaman, M., Tibajia, M.C., Aissa, M., Mah, Y., Yu, T., Meenakshisundaram, S., Heller, S., Alsukhni, R., Williams, O., Farag, M., Benger, M., Engineer, A., Bayhonan, S., Conway, S., Bhalla, A., Nouvakis, D., Theochari, E., Boyle, F., Teo, J., King-Robson, J., Law, K.Y., Sztriha, L., McGovern, A., Day, D., Mitchell-Douglas, J., Francis, J., Iqbal, A., Punjabivaryani, P., Anonuevo Reyes, J., Anonuevo Reyes, M., Pauls, M., Buch, A., Hedstrom, A., Hutchinson, C., Kirkland, C., Newham, J., Wilkes, G., Fleming, L., Fleck, N., Franca, A., Chwal, B., Oldoni, C., Mantovani, G., Noll, G., Zanella, L., Soma, M., Secchi, T., Borelli, W., Rimoli, B.P., da Cunha Silva, G.H., Machado Galvao Mondin, L.A., Barbosa Cerantola, R., Imthon, A.K., Esaki, A.S., Camilo, M., Vincenzi, O.C., ds Cruz, R.R., Morillos, M.B., Riccioppa Rodrigues, G.G., Santos Ferreira, K., Pazini, A.M., Pena Pereira, M.A., de Albuquerque, A.L.A., Massote Fontanini, C.E., Matinez Rubio, C.F., dos Santos, D.T., Dias, F.A., Alves, F.F.A., Milani, C., Pegorer Santos, B., Winckler, F., De Souza, J.T., Bonome, L.A.M., Cury Silva, V.A., Teodoro, R.S., Modolo, G.P., Ferreira, N.C., Barbosa dos Santos, D.F., dos Santos Moreira, J.C., Cruz Guedes de Morais, A.B., Vieira, J., Mendes, G., de Queiroz, J.P., Coutts, Shelagh B, Ankolekar, Sandeep, Appireddy, Ramana, Arenillas, Juan F, Assis, Zarina, Bailey, Peter, Barber, Philip A, Bazan, Rodrigo, Buck, Brian H, Butcher, Ken S, Camden, Marie-Christine, Campbell, Bruce C V, Casaubon, Leanne K, Catanese, Luciana, Chatterjee, Kausik, Choi, Philip M C, Clarke, Brian, Dowlatshahi, Dar, Ferrari, Julia, Field, Thalia S, Ganesh, Aravind, Ghia, Darshan, Goyal, Mayank, Greisenegger, Stefan, Halse, Omid, Horn, Mackenzie, Hunter, Gary, Imoukhuede, Oje, Kelly, Peter J, Kennedy, James, Kleinig, Timothy J, Krishnan, Kailash, Lima, Fabricio, Mandzia, Jennifer L, Marko, Martha, Martins, Sheila O, Medvedev, George, Menon, Bijoy K, Mishra, Sachin M, Molina, Carlos, Moussaddy, Aimen, Muir, Keith W, Parsons, Mark W, Penn, Andrew M W, Pille, Arthur, Pontes-Neto, Octávio M, Roffe, Christine, Serena, Joaquin, Simister, Robert, Singh, Nishita, Spratt, Neil, Strbian, Daniel, Tham, Carol H, Wiggam, M Ivan, Williams, David J, Willmot, Mark R, Wu, Teddy, Yu, Amy Y X, Zachariah, George, Zafar, Atif, Zerna, Charlotte, and Hill, Michael D

Published
2024
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49. Systems Thinking Approach for Production Process Optimization Based on KPI Interdependencies

Author

Winkler, Heiner, Franke, Susanne, Franke, Felix, Jabs, Iren, Fischer, Daniel, Thürer, Matthias, Rannenberg, Kai, Editor-in-Chief, Soares Barbosa, Luís, Editorial Board Member, Goedicke, Michael, Editorial Board Member, Tatnall, Arthur, Editorial Board Member, Neuhold, Erich J., Editorial Board Member, Stiller, Burkhard, Editorial Board Member, Stettner, Lukasz, Editorial Board Member, Pries-Heje, Jan, Editorial Board Member, Kreps, David, Editorial Board Member, Rettberg, Achim, Editorial Board Member, Furnell, Steven, Editorial Board Member, Mercier-Laurent, Eunika, Editorial Board Member, Winckler, Marco, Editorial Board Member, Malaka, Rainer, Editorial Board Member, Alfnes, Erlend, editor, Romsdal, Anita, editor, Strandhagen, Jan Ola, editor, von Cieminski, Gregor, editor, and Romero, David, editor

Published
2023
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